The structure-activity relationship of the interactions of SARS-CoV-2 spike glycoproteins with glucuronomannan and sulfated galactofucan from Saccharina japonica

Int J Biol Macromol. 2020 Nov 15;163:1649-1658. doi: 10.1016/j.ijbiomac.2020.09.184. Epub 2020 Sep 24.


The SARS-CoV-2 spike glycoproteins (SGPs) and human angiotensin converting enzyme 2 (ACE2) are the two key targets for the prevention and treatment of COVID-19. Host cell surface heparan sulfate (HS) is believed to interact with SARS-CoV-2 SGPs to facilitate host cell entry. In the current study, a series of polysaccharides from Saccharina japonica were prepared to investigate the structure-activity relationship on the binding abilities of polysaccharides (oligosaccharides) to pseudotype particles, including SARS-CoV-2 SGPs, and ACE2 using surface plasmon resonance. Sulfated galactofucan (SJ-D-S-H) and glucuronomannan (Gn) displayed strongly inhibited interaction between SARS-CoV-2 SGPs and heparin while showing negligible inhibition of the interaction between SARS-CoV-2 SGPs and ACE2. The IC50 values of SJ-D-S-H and Gn in blocking heparin SGP binding were 27 and 231 nM, respectively. NMR analysis showed that the structure of SJ-D-S-H featured with a backbone of 1, 3-linked α-L-Fucp residues sulfated at C4 and C2/C4 and 1, 3-linked α-L-Fucp residues sulfated at C4 and branched with 1, 6-linked β-D-galacto-biose; Gn had a backbone of alternating 1, 4-linked β-D-GlcAp residues and 1, 2-linked α-D-Manp residues. The sulfated galactofucan and glucuronomannan showed strong binding ability to SARS-CoV-2 SGPs, suggesting that these polysaccharides might be good candidates for preventing and/or treating SARS-CoV-2.

Keywords: Glucuronomannan; SARS-CoV-2; Sulfated galactofucan.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / chemistry
  • Betacoronavirus / metabolism
  • Binding Sites
  • COVID-19
  • Coronavirus Infections / virology*
  • Glucuronates / chemistry
  • Glucuronates / metabolism*
  • Heparin / chemistry
  • Heparin / metabolism
  • Humans
  • Mannose / analogs & derivatives*
  • Mannose / chemistry
  • Mannose / metabolism
  • Oligosaccharides / chemistry
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Phaeophyta / chemistry
  • Pneumonia, Viral / virology*
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • Protein Binding
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Structure-Activity Relationship


  • Glucuronates
  • Oligosaccharides
  • Polysaccharides
  • Spike Glycoprotein, Coronavirus
  • glucuronomannan
  • spike protein, SARS-CoV-2
  • Heparin
  • fucoidan
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Mannose